To determine the incidence, characteristics, causes and baseline predictors of sustained severe visual acuity (VA) loss during 2-years of anti-VEGF treatment in the Comparison of AMD Treatments Trials (CATT).

Methods

Participants were randomly assigned to treatment with ranibizumab or bevacizumab and to monthly injections for 2 years, PRN injections for 2 years, or monthly injections for 1 year and PRN injections the following year. Masked readers evaluated baseline and follow-up morphology in color fundus photographs (CFP), fluorescein angiograms (FA), and optical coherence tomography (OCT). Sustained severe VA loss was defined as VA loss of 15 letters or more from baseline at both weeks 104 and 88. Morphology features at baseline and 2 years were compared between eyes with vs. without sustained VA loss. A retina specialist reviewed image morphology to determine the likely cause of sustained VA loss.

Results

Among 1030 patients who completed 2 years of follow-up, 61 (6%) developed sustained VA loss of ≥3-lines, including 38 (4%) with sustained VA loss of ≥6-lines. At 2 years, eyes with sustained VA loss had more scarring and geographic atrophy (GA) on CFP and FA especially in the foveal center, and lesions were approximately twice as large (Table 1). On OCT at 2 years, the proportions with intraretinal fluid, subretinal fluid, retinal thinning/thickening, or subretinal hyper reflective material were higher, and retinal thickness or sub-RPE thickness were greater (Table 1). The cause of sustained VA loss included foveal scarring (41%), GA (12%), RPE tear (5%). Most of the remainder (28%) had non-elevated pigmentary abnormalities, some with retinal thinning (15%), and some with retinal thickening (7%). Independent baseline risk factors for sustained VA loss were the presence of GA, larger area of CNV, and bevacizumab treatment (Table 2).

Conclusions

Among CATT participants, sustained VA loss of ≥3-lines occurred in 6% of patients. The development of scar or GA in the fovea center contributed to the majority of the sustained VA loss after 2 years of treatment with ranibizumab or bevacizumab. Treatment targeting the prevention of scar or GA may improve the VA outcomes of anti-VEGF treatment.